Lipopolysaccharide induces cell volume increase and migration of dendritic cells

ABSTRACT Migration of dendritic cells (DCs) plays an important role in T‐cell‐mediated adaptive immune responses. Lipopolysaccharide (LPS) sensed by Toll‐like receptor 4 (TLR4) serves as a signal for DC migration. We analyzed LPS‐induced DC volume changes preceding the directed movement towards chemoattractants. Treatment with LPS resulted in rapid, prolonged cell swelling in wild‐type (WT), but not in TLR4−/− bone marrow‐derived (BM) DCs indicating that TLR4 signaling is essential for LPS‐induced swelling. As a consequence, LPS‐treatment enhanced the migratory activity along a chemokine (CCL21)‐gradient in WT, but not in TLR4‐deficient BMDCs suggesting that the LPS/TLR4‐induced swelling response facilitates DC migration. Moreover, the role of calcium‐activated potassium channels (KCa3.1) as putative regulators of immune cell volume regulation and migration was analyzed in LPS‐challenged BMDCs. We found that the LPS‐induced swelling of KCa3.1‐deficient DCs was impaired when compared to WT DCs. Accordingly, the LPS‐induced increase in [Ca2+]i detected in WT DCs was reduced in KCa3.1‐deficient DCs. Finally, directed migration of LPS‐challenged KCa3.1‐deficient DCs was low compared to WT DCs indicating that activation of KCa3.1 is involved in LPS‐induced DC migration. These findings suggest that both TLR4 and KCa3.1 contribute to the migration of LPS‐activated DCs as an important feature of the adaptive immune response.